Biological and induction effects of phenobarbital and 3-methylcholanthrene in mink (Mustela vison)

Mink were injected (ip) daily with 20 mg/kg of 3-methylcholanthrene (MC) or 40 mg/kg of phenobarbital (PB) for 3 days and killed 48 hr after the last injection. The duration of anesthetic action of PB increased after each injection. MC-treated mink became anorexic and lost substantial body weight. PB caused enlargement of liver and lungs, whereas MC caused liver atrophy. No major treatment-related morphologic changes including amount of endoplasmic reticulum (ER) in liver were revealed by electron microscopic examination. Microsomal protein content was not increased and NADPH cytochrome P-450 reductase was not induced in liver by either PB or MC. Cytochrome P-450 (448) was increased 3.2-fold by PB and 2.5-fold by MC. Cytochrome b5 was increased 2.3-fold by MC but was not affected by PB. Aminopyrine N-demethylase was enhanced 5.1-fold in activity by PB whereas hexobarbital hydroxylase was not induced. MC-treatment moderately increased the activities of benzo(a)pyrene hydroxylase (1.7-fold) and ethoxyresorufin O-deethylase (2.1-fold) but had no effect on ethoxycoumarin O-deethylase. The most distinctive features of the mink revealed by this study are a) lack of PB induction of the ER, microsomal protein content, NADPH-cytochrome P-450 reductase, and hexobarbital hydroxylase, and b) lack of MC induction of cytochrome P-448-associated mixed function oxidases that are known to be highly responsive to MC in other species.